This Core will maintain existing lines of transgenic (and other) mice and will provide animals of various ages (from embryos to aged adults) to projects within this program. The Core will also work with investigators of the Program Project to to develop new lines of mice relevant to their projects. Animals with transgenic expression of wild type and mutant PS1, animals under development expression aph-1 and pen-1, and animals lacking PS1 (embryos or neuronal cultures) will be used in Project 1 to examine effects on the levels and stability of the other gamma-secretase components (aph-1, pen-2 and nicastrin). In Project 3, these animals will be used to study the effects of these transgenes on the competition between APP and Notch as substrates for gamma-secretase and on the interactions between gamma-secretase and its substrate. In Project 5 and Project 6, these animals will be used to assess the contribution of each of these proteins to the cleavage of other gamma-secretase substrates. Design and generation of additional transgenics will be performed in collaboration with Project 6 (APLP1 and APLP2) and, potentially, with Project 5 (Nectin-1). Additionally, animal husbandry services will be provided for investigators as needed. By consolidation of efforts involving animals, the Program Project seeks to have efficient use of mice, through the coordination of requests from different investigators and sharing of the animals when possible. This will help to keep animal numbers and costs are kept as low as possible while ensuring that, within the limits of colony space, the needs of investigators in all projects are met. Animals from this Core are also made available, as possible, to investigators outside of the Program Project.